This project is designed to prepare a GMP quality investigational filovirus vaccines and complete the preclinical and laboratory studies needed to begin clinical trials. The Vaccine Research Center (VRC), NIAID is developing a vaccine strategies directed at filoviruses such as Marburg and Ebola for which there are no current preventive vaccines and no available therapy. These viruses are associated with sporadic natural outbreaks as well as the potential to be used as bioterrorism attacks. The vaccine candidates are designed to elicit immune responses to viral sequences from viruses isoalted from the most recent outbreaks. In November 2003, the VRC Clinical Trials Core launched a Phase I clinical study (VRC 204) of a multigene DNA Ebola vaccine at the NIH Clinical Center (Bethesda, MD) as the first step in developing these products regimen. The trial completed entollment and a next-generation Ebola DNA vaccine as well as a Marburg DNA vaccine was manufactured and completed nonclinical testing. Clinical evaluation of the Marburg DNA vaccine has begun. These vaccines will be evaluated clinically as single agents and as part of a DNA prime-adenovector boost regimen.